SCHNEIDER, EVANS, AND FRYER
2604 J . Org. Chem., Vol. 37, No. 16, 1972 slowly. The mixture was allowed to reflux overnight, hydrolyzed, and worked up in the usual manner to yield 2.29 g (0.0042 mol, 857,) of pale yellow crystals: mp 245-248"; ir (CCl,) 3635 em-' (OH); nmr (CClr) 7 3.10 (m, 30, ArH), 4.50 (s, 1, OH), 7.26 (s, 1, CH). Anal. Calcd for C41H320: C, 91.07; H, 5.96; mol wt, 540. Found: C, 90.78; H, 6.06; mol wt, 540 (mass spectrum). 1,2,3,4,5,5-Hexaphenyl-1,3-~yclopentadiene~ (X). A. Using Acetyl Chloride.-Into a 100-ml round-bottomed flask equipped with a condenser was placed 1.00 g (1.8 mmol) of IX and 25 ml of acetyl chloride, and the mixture was refluxed for 24 hr. After cooling to room temperature the mixture was carefully diluted with 100 ml of water and extracted with benzene and the benzene was dried over magnesium sulfate. Removal of the solvent under vacuum afforded a yellow oil which was crystallized from benzene and ethanol to yield 0.88 g (1.68 mmol, 96.5%) of white crystals: mp 175-177' (lit.1 mp 172'); uv (CH,CN) 335, 275 (sh), 247 mp.
Anal. Calcd for CllH30: C, 94.21; H, 5.77; mol wt, 522. Found: C, 94.27; H, 5.93; mol wt, 522 (mass spectrum). B. Using Acetic Anhydride.-Using the same procedure and amounts of reagents as described above but allowing the mixture to reflux for 3 days afforded 90% of product identical with that described above.
Registry No.-111, 2137-74-8;IV, 34759-47-2;VIII, 34759-48-3;IX,34759-49-4;X,34759-50-7. Acknowledgments.-We thank the donors of the Petroleum Research Fund, administered by the American Chemical Society, for partial support of this research. We also wish to thank the College of Arts and Sciences at VPI and SU for a Small Projects Grant which also helped support this research.
The Synthesis and Transformations of 2-Nitro-1-phenyl-1-hydroxyindene and Its Isomer J. SCHNEIDER, E. L. EVANS, AND R. IAN FRYER* Hoffmann-La Roche, Inc.,Nutley, New Jersey 07110 Received January 19, 197'2 Condensation of 2-benzoylbenzaldehyde (1) with nitromethane in the presence of sodium methoxide gave, after acidification, 2-nitro-1-phenyl-1-hydroxyindene (3), 2-nitro-3-phenyl-1-hydroxyindene (4),and 2-nitro-lphenyl-1,3-dihydroxyindan(5). The first two compounds were converted to the corresponding acetates 7 and 8, which on treatment with primary or secondary amines gave the nitroenamines 9 and the ammonium salts 11 of the 2-nitro-1-phenyl-3-indanone (12),respectively. Hydrolysis of 9 or 11 afforded 12. Treatment of the acetate 7 with alcohols yielded 2-nitro-3-phenyl-1-alkoxyindene(17). After prolonged reflux the isomeric 2-nitro-lphenyl-3-alkoxyindene (18)was obtained. A catalytic amount of triethylamine rearranges 17 to 18.
SCHEME I The condensation of 1,4, 1,5, and 1,6 dialdehydes with nitromethane in an alkaline medium followed by acidification is a general method for the synthesis of five-, six-, and seven-membered ring systems.' However, little is known about the reactivity of diketones or keto aldehydes toward nitr0methane.l This led us 2 to study the condensation of o-benzoylbenzaldehyde2 with nitromethane under alkaline conditions. Treatment of o-benzoylbenzaldehyde with nitromethane in the presence of 1 equiv of sodium methoxide in methanol generated within 2 min a white, crystalline precipitate of the l-phenyl-l,3-dihydroxy-2-acinitroindan sodium salt 2. Acidification of 2 with sulfuric acid in ice yielded two isomeric 2-nitrophenylhydroxyindenes (3 and 4) as well as 2-nitro-l-phenyl-1,3-dihydroxyindan ( 5 ) . Structures were readily assigned from an interpretation of the nmr spectra for the three compounds. Dehydration of 5 with p-toluenesulfonic acid in refluxing benzene gave a mixture consisting mainly of 4 and a small amount of 3. Treatment of either 3, 4, or 5 with sulfuric acid in benzene as dehydrating agent gave 1,3-diphenyl-2-nitroindene (6) (Scheme I). Acetylation of 3 was found to be temperature dependent. At -5', the acetate 7 was obtained usually CEH3 accompanied by 8. The thermodynamically more stable product 8 was produced either at room tempera6 ture from 3, by direct acetylation of 4, or by treatment Addition of primary or secondary amines to a soluof 7 with glacial acetic acid a t room temperature tion of 7 resulted in an immediate color change from (Scheme II), light yellow to green with the formation of nitroen(1) F. W. Liohtenthrtler, Angew. Chem., Int. Ed. E n d . , 3, 211 (1964). amines of type 9.4 Most likely Michael addition with (2) W. Metlesics, T. Anton, M. Chaykovsky, V. Toome, and L. H. Sternbaoh. J . Ora. Chem.. 33. 2874 (1968). (3) C . F: Koelsch, ibid., 26, 4238 (1961).
(4) See also F. W. Lichtenthaler and N . Majer, Tetrahedron Lett., 411 (1969).
J. Org. Chem., Vol. 37, No. 16, 1972
%NITRO- 1-PHENYL- 1-HYDROXYINDENE
2605
SCHEME I1
Ji 13
trated by the expeditious rearrangement of 17a to 18a in the presence of a catalytic amount of triethylamine (Scheme IV).
SCHEME 111 R’
7-
SCHEME IV
HNRR’
- 9
C
HNRR‘
CH,
I
c= 0
I
PR
HNRR’
b
f
N(Et),
or EtOHlA
188,b
a, R = E t b, R = Me
HNRR‘
HB+
17a,b
11
0
16
C6Hj
immediate loss of acetic acid leads to an intermediate like 15 (Scheme 111) which then rearranges to 9. If a leaving group less active than acetate is present, e.g., the hydroxyl group in 3, the reaction sequence stops a t the Michael adduct. Thus, treatment of 3 with morpholine leads to compound 10. However, the reaction will proceed to 9a if the hydroxyl group is converted into a good leaving group by protonation with phosphoric acid. The transformation of intermediate 15 t o compound 9 is facilitated by bases as was illus(5) A. M. Weidler, Acta Chem. Scand., 17, 2724 (1963); G.Bergson and A. M . Weidler, ibid., 18, 1487, 1498 (1964); C. Ohlson, J. Wollmark, and G . Bergson, ibid., 20, 750 (1966).
19
When the isomeric acetate 8 was treated with primary or secondary amines only a small amount of 9 was formed. The major products were the ammonium salts 11 of 2-nitro-1-phenylindanone (12). A possible reaction sequence is indicated in Scheme I11 with the initial formation of the enol acetate 16, followed by ready cleavage t o 9 or 11 by attack of the nucleophile of Ca (path a) or on the carbonyl function of the acetoxy group (path b) , respectively. Direct nucleophilic displacement of the acetoxy group in 8 would also lead to 9 (path c) via. the intermediate 15. These mechanisms
2606
J. Org.Chem., Yol. 37, No. 16,1973
SCHNEIPER, EVANS, AND FRYER
were clarified by the isolation of the unstable intermediate 16, obtained by treatment of 8 with catalytic amounts of triethylamine. Reaction of 16 with morpholine gave exclusively l l a . No trace of 9 could be detected by tlc, thereby excluding path a. Compound 11 must be derived from 8 as indicated by path c. The formation of the intermediate 16 is analogous to the facile rearrangement of 4 to l l a with morpholine. Hydrolysis of 9 or acidification of 11 led to 12. We found that the unsubstituted 2-nitroindenone (14)6 was also formed in fair yield by treatment of the 1hydroxy-2-nitroindene (13)' with 1 equiv of triethylamine followed by immediate acidification. The ease of formation of nitroenamines from 7 prompted us to investigate the products resulting from the treatment of this compound with alcohols. Two types of compounds +ere obtained, the adducts 17 and the rearranged compounds 18 (Scheme IV). Prolonged reflux of the reaction mixture led to a high percentage of the rearranged product. This transformation seems to proceed in polar solvents more rapidly than in nonpolar solvents. After 16 hr reflux in ethanol, a pure sample of 17a was converted to 18a in 77% yield, whereas reflux in toluene for the same period of time led t o only 17% of the rearranged product as estimated by nmr. As mentioned above, this rearrangement was facilitated by the presence of a catalytic amount of triethylamine. The structural assignment for 18 was based on the signal for Hd at 0.3 ppm downfield of the aromatic region in the nmr spectrum. This would be expected because of the presence of syn axial heteroatoms at CB. I n the case of the nitroenamines 9, an even stronger deshielding of 0.4 ppm was observed. The structure of 18 was further substantiated by the methylation of 12 with diazomethane to give 18b and the nitronic ester 19.8
Anal. Calcd for ClsHlaNO4: C, 66.41; H , 4.83; N, 5.16. Found: C, 66.16; H, 4.99; N, 6.13. The filtrate was evaporated and treated with 15 ml of a mixture of hexane and ethyl acetate (2: 1). The product formed yielded, after washing with the above mixture, 3.51 g of 3 as rectangular plates, mp 118.5-120'. Repetition of the above procedure gave an additional 1.44 g of 3, mp 117-120', for a combined yield of 4.95 g (.79.1%), nmr (CDCla) S 3.72 (broad s, 1, OH), 7.60 (m, 9, ArH), 8.01 (s, 1, vinyl Ha). Anal. Calcd for C15HllN03: C, 71.14; H , 4.38; N, 5.53. Found: C, 71.08; H,4.59; N, 5.69. Evaporation of the above filtrate yielded Rn oil, which was extracted several times with 100-ml portions of boiling cyclohexane. The combined cyclohexane solutions were evaporated to a residue and barely dissolved in a small amount of methylene chloride. On addition of a mixture of hexane and ethyl acetate ( 2 : l ) and cooling, 390 mg (3.1%) of yellow, clustered prisms of 4 were collected, mp 121-124', nmr (CDCl,) 6 3.50 (broads, 1, OH), 3.90 (s, 1, HI), 7.57 (m, 9, ArH). Anal. Calcd for Cl5HI1NOa: C, 71.14; H , 4-38; N, 5.53. Found: C, 71.44; H , 4.50; N, 5.47. 2-Nitro-3-phenyl-1-hydroxyindene (4).-A mixture of 12 g (44.3 mmol) of 5 and 1 g of toluenesulfonic acid was refluxed for 1.5 hr. After evaporation, the obtained residue was recrystallized from methylene chloride-hexane to give a mixture of 3 and 4 as the first crop. Concentration of the mother liquor yielded 5.55 g of 4. Recrystallization from methylene chloride-hexane afforded 4.84 g (43.2%) of yellow prisms, mp and mmp 121123.5'. 2-Nitro-l,3-diphenylindene(6).9-A solution of 250 mg (0.92 mmol) of 5 in 12 ml of benzene was mixed with 0.6 ml of concentrated sulfuric acid and refluxed for 1.25 hr. The cold solution was extracted three times with 70-ml portions of water, dried over sodium sulfate, filtered, and evaporated. The residue was recrystallized from ether-petroleum ether (bp 30-60') to give 210 mg (73%) of 6 as yellow prisms, mp 105-107', nmr (CDCla) S 5.36 (1, s , HI), 7.1-7.6 (m, 14, ArH). Anal. Calcd for C21H1SN02:C, 80.49; H , 4.83; N, 4.47. Found: C, 80.56; H , 5.04; N, 4.43. 2-Nitro-1-phenyl-I-acetoxyindene(7).-A slurry of 40.5 g (160 mmol) of 3 in 100 ml of acetic anhydride was cooled to - 5 to lo', and then 1 ml of concentrated sulfuric acid was added to the vigorously stirred mixture. After 45 min, the temperature was allowed to rise to 0'. The yellow plates formed were collected and washed well with a mixture of hexane and ethyl acetate (2 : 1) to give 32.0 g (67.7%) of 7, mp 140-144'. RecrystalExperimental Section lization from benzene afforded the analytically pure material, mp 148-150', nmr (CDCl,) 6 2.17 (s, 3, CHa), 6.3 (m, 9, ArH), Melting points were taken on a Thomas-Hoover melting point 7.94 (s, 1, vinyl Ha). apparatus and are corrected. The uv spectra were determined Anal. Calcd for CI7HlaNO~:C, 69.15; H , 4.44; N , 4.74. on a Cary Model 14 spectrophotometer, nmr spectra with a Found: C,69.42; H,4.36; N,4.71. Varian A-60 instrument, and the ir spectra on a Beckman IR-9 2-Nitro-3-phenyl-1-acetoxyindene (8). A.-To a solution of spectrophotometer. All spectra were compared in order to 10 g (39.5 mmol) of 3 in 20 ml of acetic anhydride was added 0.1 confirm or exclude the expected structural changes. ml of concentrated sulfuric acid at room temperature. The dark 1,J-Dihydroxy- 1-phenyl-2-acinitroindanSodium Salt (2) .-To brown solution was stirred for 30 min and then evaporated. a solution of 10.5 g (50 mmol) of o-benzoylbenzaldehyde and 6.1 The residue was treated with ice and saturated sodium bicarg (100 mmol) of nitromethane in 50 ml of methanol was added 50 bonate solution. The resulting precipitate was filtered, washed ml of 1 iV sodium methoxide solution in methanol. The resultwell with water, dissolved in methylene chloride, dried over aning white precipitate was stirred for 30 min, and after the addihydrous magnesium sulfate, filtered, and evaporated. Addition tion of 100 ml of ether was collected on a funnel and washed with of ether afforded 8.3 g of 8, mp 115-120'. Recrystallization ether, uv max (0.01 N KOH) 256 mp (e 10,960), 268 (9800), from ethanol gave 6.2 g (53.2%) of dark yellow prisms, mp 128274..5 (10,200). 131', nmr (CDCla) 6 2.20 (s, 3, CHs), 7.06 (s, 1, HI), 7.5 (m, 9, 2-Nitro-I-phenyl-1-hydroxyindene (3). 2-Nitro-3 phenyl - 1hydroxyindene (4), and P-Nitro-l-phenyl-l,3-dihydroxyindan ArH). Anal. Calcd for C ~ ~ H ~ ~ NC, O I89.15; : H, 4.44; N, 4.74. (5).-The above prepared salt was suspended in 100 ml of water Found: C, 69.10; H,4.48; N,4.64. and, with stirring, 30 g of ice and 10 ml of concentrated sulfuric B.-To a solution of 200 mg (0.79 mmol) of 4 in 2 ml of acetic acid were poured into the reaction mixture. After 30 min of anhydride was added 1 drop of concentrated sulfuric acid a t room stirring, 100 ml of methylene chloride was added and the organic temperature. After 20 min of stirring, the mixture was poured layer was separated, dried over anhydrous sodium sulfate, into ice and saturated sodium bicarbonate solution. The crystalfiltered, and concentrated in uacuo to a viscous oil. On addition line, orange precipitate, 210 mg, mp 119-123', was recrystallized of 30 ml of benzene and standing, a white solid appeared which from methylene chloride-hexane to give 100 mg (42.9%) of 8, was collected and rinsed with benzene to give 3.91 g (28.8%) of mp and mmp 127-131°. 5 as white rods, nmr (CDCla)6 5.32 (s, 2, OH), 5.38, 5.68 (2 d, C.-A solution of 100 mg (0.34 mmol) of 7 in 3 ml of acetic 2 X 1, CHCH), 7.15 (m, 9, ArH). acid was stirred overnight a t room temperature. On dilution with ice and water, a reddish yellow crystalline solid (70 mg) (6) T. Kametani, H. Sugakara, and S. Asagi, Chem. Pharm. Bull., 14, 1408 was obtained, mp 120-126', which on recrystallization from (1966); H.H.Baer and S.R . Naik, J. Ore. Chem., 86, 2927 (1970). ethyl acetate and hexane gave 8, mp and mmp 127-128.5'. (7) J. Thiele and E. Weitz, Justus Liebigs Ann. Chem., 877, 1 (1910);
-
-
F. W. Liohtenthaler, Tetrahedron Lett., 775 (1963); H. H. Baer and B . Aohmatowioz, J. Org. Chem.. as, 3180 (1964). (8) The stereochemistry of this compound has not been established.
(9) The formation of 8 was also observed from S and 4 under the same reaction conditions.
2-NITRO-1-PHENYL-1-HYDROXYINDENE
2-Nitro-I-phenyl-3-morpholinoindene (9a). A.-A solution of 8 g (27.1 mmol) of 7 in 60 ml of acetone was mixed with 4.7 g (54.5 mmol) of morpholine in 10 ml of acetone. After 45 rnin of stirring a t room temperature, ice and water were added. The precipitate collected was recrystallized from methylene chloride-hexane to give 6.29 g (72.1Oj,) of Pa as deep yellow prisms, mp 205-206' dec, nmr (CDCls) 6 3.92 (m, 8, aliphatic H), 5.18 (8, 1, HI) 7.22 (m, 8, ArH), 7.72 (m, 1, H,). Anal. Calcd for C18H18NzOa: C, 70.79; H , 5.63; N, 8.69. Found: C, 70.92; H, 5.75; N, 8.64. B.-A mixture of 550 mg (1.62 mmol) of 2-nitro-3-morpholino1-hydroxy-1-phenylindane(10) and 3 g of 85% phosphoric acid was heated on the steam bath for 10 rnin until a clear brown solution was present. After dilution with water, insoluble solids were filtered off. The filtrate was made basic with concentrated sodium hydroxide solution and then extracted with 75 ml of chloroform. The organic layer was separated, dried over anhydrous sodium sulfate, and evaporated to dryness to give on addition of methanol 180 mg of yellow prisms, mp and mmp 208210'. The above insoluble solid was dissolved in chloroform and washed with dilute sodium hydroxide solution. The organic layer was worked up as above to give 100 mg of crude material, mp and mmp 199-205'. A total of 280 mg (53.6%) of 9a was obtained. 2-Nitro-1-phenyl-3-benzylaminoindene(9b).-This compound was prepared using the same procedure as described for 9a, method A, in 91% yield as yellow prisms from methylene chloride-ethanol, mp 180-181', nmr (CDC13) 6 5.10 (9, 2, CHI), 5.20 (6, I , HI), 7.22, 7.40 (m, 13, ArH), 7.85 (m, 1, H,), 10.28 (broad s, 1, NH). Anal. Calcd for C22H18NzOz: C, 77.18; H, 5.30; N , 8.18. Found: C, 76.88; H, 5.24; N, 8.16. 2-Nitro-3-morpholino-I-hydroxy-1-phenylindan(lo).-To a solution of 2.53 g (1 mmol) of 3 in 15 ml of tetrahydrofuran was added a small excess of morpholine in 5 ml of tetrahydrofuran. After 30 rnin of stirring at room temperature, the mixture was concentrated to ca. 1/3rd of the volume and diluted with 25 ml of ether. The product formed was collected to give 2.58 g (76%) of white prisms, mp 172' dec. Recrystallization of a sample from tetrahydrofuran-chloroform afforded the analytically pure product, mp 171-172' dec, nmr (DMSO) 6 2.52, 3.63 (m, 2 X 4, aliphatic H), 5.47 (9, 2, CHCH), 6.56 (s, 1, OH), 7.37 (m, 9, ArH). Anal. Calcd for Cl&hoN2O4: C, 67.05; H, 5.92; N , 8.23. Found: C, 67.28; H , 5.96; N, 8.23. Morpholinium 1-Phenyl-3-indanone-2-nitronate(1 la). A.A solution of 20 g (67.8 mmol) of 8 in 150 ml of methylene chloride was added dropwise to a solution of 12 g (138 mmol) of morpholine in 80 ml of methylene chloride. The thick white precipitate which formed was collected after 40 rnin and washed well with methylene chloride. The filtrate wa8 set aside. The salt obtained (18.7 g) was recrystallized from hot dimethylformamide to give 12.9 g (56%) of l l a as white needles: mp 204' dec; ir (KBr) 2800-2480 cm-I (amine salt); nmr (DMSO) 6 3.17, 3.83 (m, 2 X 4, aliphatic H), 4.96 (s, 1, HI), 6.9-7.66 (m, 9, ArH). Anal. Calcd for C19H20N204:C, 67.05; H, 5.92; N, 8.23. Found: C, 66.94; H , 6.00; N, 8.22. The above filtrate was washed with water, dried over anhydrous sodium sulfate, filtered, and evaporated. The residue was recrystallized from methylene chloride-carbon tetrachloride to give 2.0 g (9%) of 9a as deep yellow prisms, mp and mmp 208210' dec. B.-A solution of 590 mg (2 mmol) of 2-nitro-l-phenyl-3acetoxyindene (16) in a 5 ml of methylene chloride was added dropwise to a solution of 348 mg (4 mmol) of morpholine in 2 ml of methylene chloride. After 10 min, the precipitate was collected to give 622 mg (91.5%) of I l a as white needles, mp and mmp 196-199' dec. The methylene chloride filtrate was washed with water and dried over anhydrous sodium sulfate. Tlc of this solution, compared with 9a using hexane-ethyl acetate (1: 1) as eluent showed no trace of 9a. C.-To a solution of 100 mg (0.39 mmol) of 4 in a minimum amount of tetrahydrofuran was added 86 mg of morpholine. After the solution had stood for 30 min, the white precipitate formed was filtered off and washed well with ether to give 135 mg (100%) of l l a , mp and mmp 198-199' dec. Benzylammonium l-Phenyl-3-indanone-2-nitronate(1l b ) .Following procedure A for l l a this compound was prepared
J. Org. Chern., Vol. 37, No. 16, 1972
260'7
similarly in 52.4% yield as pale yellow needles recrystallized from hot dimethylformamide: mp 200-203' dec; ir (KBr) 28002480 cm-l (amine salt); nmr (DMSO) 6 4.10 (s, 2, CH,), 4.98 (s, 1, HI), 7.17,7.38 (m, 14, Ar H ) , 8.62 (broads, 3, NHa). Anal. Calcd for CZZHZONZO~: C, 73.31; H, 5.59; N, 7.77. Found: C,73.32; H , 5.61; N, 7.82. A by-product, 9b, was obtained in 22.4% yield as yellow needles, mp and mmp 180-183' dec. 2-Nitro-1-phenyl-3-acetoxyindene (16).-To a solution of 2.95 g (10 mmol) of 8 in 10 ml of anhydrous methylene chloride was added 0.05 ml of triethylamine. The solvent was evaporated after 10 min. The residue was treated with ether and petroleum ether to give 2.44 g of a light tan solid. Recrystallization from methylene chloride-ether-petroleum ether afforded 1.35 g (45.8%) of 16 as colorless needles, mp 96-98' dec, nmr (CDCL) 6 2.37 (8, 3, CH3), 5.23 (s, 1, HI), 7.2-7.75 (m, 8, ArH), 7.95 (m, 1, H4). Anal. Calcd for Cl7HI8NOI: C, 69.15; H, 4.44; N, 4.74. Found: C,69.34; H,4.51; N, 5.04. 2-Nitro-1-phenyl-3-indanone(12). A.-A slurry of 500 mg (1.47 mmol) of I l a in 30 ml of ethanol and 50 ml of 2 N hydrochloric acid was warmed on the steam bath for 5 min. The organic solvent was evaporated and the aqueous residue was extracted with methylene chloride. The organic layer was dried over anhydrous sodium sulfate, filtered, and evaporated. The residue obtained was recrystallized from ether-petroleum ether to give 270 mg (73%) of white rods: mp 93-96'; ir (KBr) 1745 cm-' (CO); nmr (CDC13) 6 5.26, 5.40 (AB, J = 5 Hz, 2, CHCH), 7.0-8.0 (m, 9, Ar H). Anal. Calcd for C I ~ H ~ ~ NC, O ~71.14; : H, 4.37; N , 5.53. Found: C, 71.15; H,4.36; N, 5-53. B.-A solution of 250 mg (0.77 mmol) of 9a in 50 ml of ethanol was treated with 100 ml of 2 N hydrochloric acid on the steam bath until the solution was completely discolored. The reaction was worked up as above to give 85 mg (44%) of crystalline material, mp and mmp 89-93'. 2-Nitro-1-indanone (14).-To a slurry of 3.54 g (20 mmol) of 2nitro-1-hydroxyindene (13)in 13 ml of tetrahydrofuran was added 2.02 g (20 mmol) of triethylamine in 2 ml of tetrahydrofuran. After 4 min, 45 ml of water was added to the green solution and the pH was adjusted to 6 with 2 iV aqueous hydrochloric acid. This solution was extracted three times with 30 ml of ether. The ethereal layers were discarded. The aqueous layer was cooled in an ice bath and acidified with 2 N hydrochloric acid to pH 2.5. A crystalline precipitate appeared and was collected to give 2.25 g, mp 70-75'. The solid was extracted into 1 1. of boiling petroleum ether (bp 60-90'), which was decanted from insoluble material and evaporated. Recrystallization of the residue from isopropyl alcohol-petroleum ether gave 1.05 g (30%) of pale yellow rods, mp 77-80'. A second crop of 300 mg, mp 75-77', was obtained from the filtrates, nmr (CDC13) 6 3.78 (m, 2, CH,), 5.48 (9, 1, Hz), 7.15-7.90 (m, 4, ArH). Anal. Calcd for C9H7NOs: C, 61.01; H, 3.98; N, 7.91. Found: C, 61.05; H,4.03; N, 7.82. 2-Nitro-3-phenyl-I-ethoxyindene (17a). A,-A solution of 5.9 g (20 mmol) of 7 in 100 ml of ethanol was refluxed for 2 hr and then evaporated. The residue was taken up in 70 ml of ether and washed three times with 100-ml portions of water. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The product crystallized on addition of ether and petroleum ether. After two recrystallizations from ethanol, 2.6 g (46%) of 17a was obtained as yellow, clustered needles, mp 81.5-83'. From the filtrates, an additional 830 mg of less pure material, mp 79-81.5", was isolated, nmr (CDC13) 6 1.25 (t, 3, CHa), 3.75 (9, 2, CH20),5.82 (s, 1, HI), 7.58 (m, 9, ArH). Anal. Calcd for CI7Hl5NO3: C, 72.58; H , 5.37; N , 4.98. Found: C, 72.82; H, 5.48; N,4.92. 2-Nitro-3-phenyl-I-methoxyindene (17b).-A solution of 10.6 g (36 mmol) of 7 in 150 ml of methanol was refluxed for 1.5 hr. On concentration and cooling, 7.88 g (82%) of 17b was collected as yellow rods, mp 113-114'. A second crop (630 mg) of less pure material, mp 112-113", was obtained from the mother liquor. Recrystallization of a sample from methanol afforded an analytically pure product, mp 113-114.5', nmr (CDCl,) 6 3.41 (s, 3, CHaO), 5.74 (s, 1, HI), 7.49 (m, 9, ArH). Anal. Calcd for CIBHl3NO3: C, 71.90; H, 4.90; N, 5.24. Found: C, 71.77; H,5.01; N,5.17. 2-Nitro-1-phenyl-3-ethoxyindene (18a). A.-A solution of
2608 J . Org. Chem., Vol. 3'7, No. 16, i97.2
FENDLER AND LARSEN
295 mg (1 mmol) of 7 in 30 ml of ethanol was refluxed for 23 hr. Evaporation of the solvent and crystallization of the residue from an ether-ethanol mixture gave 154 mg of a crude mixture of 17a and 18a (by nmr). Several recrystallizations from ethanol finally afforded a pure sample (29 mg, 10.3%) of 18a as yellow prisms, mp 88.5-90.5", nmr (CDCla) 6 1.52 (t, 3, CHa), 4.76 (AB of q, 2, CHsO), 5.18 (s, 1, HI), 7.29 (m, 8, ArH), 7.73 (m, 1 , H4). Anal. Calcd for CI~HISNO~: C, 72.58; H, 5.37; N, 4.98. Found: C, 72.49; H, 5.38; N, 5.01. B.-To a solution of 50 mg (0.18 mmol) of 17a in 5 ml of methylene chloride was added 1 drop of triethylamine. The solvent was evaporated after 5 min and the crystalline residue was treated with ether and petroleum ether to give 35 mg (70aj,) of 18a as yellow prisms, mp and mmp 88-90'. 2-Nitro-1-phenyl-3-methoxyindene(18b). A.-18b wa8 similarly prepared (see 18a, procedure A) in 3.8% yield as yellow prisms, mp and mmp 99-102', after several recrystallizations from ethanol. B.-A solution of 5 g (19.75 mmol) of 12 in 100 ml of ether was treated with an excess of ethereal diazomethane solution until no more starting material was present as determined by tlc. Evaporation of the solvent gave an off-white, crystalline solid which on recrystallization from ethyl acetate-ether gave 0.85 g of pale yellow prisms, mp 121-122', which were identified as 1phenyl-2-methoxyimino-3-indanone N-oxide (19),ir (CHCL) 1700 cm-" (CO), nmr (CDCla) 6 3.88 (s, 3, CHaO), 5.07 (s, 1 , HI), 7.0-7.65 (m, 8, ArH), 7.90 (m, 1, HI). Anal. Calcd for CleHlaNOa: C, 71.90: H, 4.90; N, 5.24. Found: C, 72.03; H, 5.11; N, 5.25.
The residual mother liquors and filtrates were combined and evaporated and the residue was chromatographed on 400 g of silica gel using hexane-ethyl acetate (2: 1 ) as the eluent. Removal of solvent from the first fractions, gave an additional 390 mg of 19, for a combined yield of 1.24 g (23.5%), mp and mmp 121-122'. Later fractions gave, after removal of the solvent, 2.2 g (42%) of 18b as yellow prisms (crystallized from ethyl acetate-ether), mp 91.5-93', reset mp 101-102', nmr (CDC13) 6 4.37 (s, 3, CHaO), 5.10 (8, 1, HI), 6.9-7.45 (m, 8, ArH), 7.70 (m, 1, H4). Anal. Calcd for C16H13NOa: C, 71.90; H, 4.90; N, 5.24. Found: C, 71.95; H,4.94; N,5.28.
Registry No. -2, 34764-52-8; 3, 34764-53-9; 4, 34764-54-0; 5 , 34764-55-1 ; 6, 34764-56-2; 7, 3476457-3; 8, 34789-54-3; 9a, 34764-58-4; 9b, 34764-59-5; 10, 34764-60-8; 1 la, 34764-61-9; 1 lb, 34764-62-0; 12, 34764-63-1; 14, 13943-70-9; 16, 34764-65-3; 17a, 34764-66-4; 17b, 34764-67-5; 18a, 34764-68-6; lab, 34764-69-7 ; 19, 34764-70-0. Acknowledgment.-The authors are indebted to the following members of the Physical Chemistry Department under the direction of Dr. P. Bommer: Dr. F. Scheidl for the microanalyses, Dr. T. Williams for the nmr spectra, Dr. V. Toome for the uv spectra, and Mr. S. Traiman for the ir spectra.
Thermodynamic and Kinetic Analysis of Meisenheimer Complex Formati on J. H. F E N D L E R * ~ * AND JOHNW. LARSEN'~ Department of Chemistry, Texas A & M University, College Station, Texas 77843, and Department of Chemistry, University of Tennessee,Knoxville, Tennessee 37916 Received February 22, 1971 The free-energy change for the reaction of sodium methoxide with 2,4,6-trinitroanisole (3)to give the Meisenheimer complex 2 has been measured and combined with the heat of this reaction to give the entropy change in DMSO-methanol mixtures. Using solubility measurements, the activity coefficients of 3 and the complex 2 have been determined. The free energy, enthalpy, and entropy of transfer of 3 and its complex 2 from pure methanol to methanolic dimethyl sulfoxide solutions have been calculated. The solvent effect on the thermodynamics of the reaction between sodium methoxide and 3 has been measured. The degenerate activity coefficients of sodium methoxide in methanol-DMSO mixtures have been obtained using an indirect method.
The chemistry of Meisenheimer or u complexes, most of which are substituted cyclohexadienylide ions, has recently come under renewed scrutiny2 and this research area has been quite active. Dipolar aprotic solvents have been found to enhance the stability of Meisenheimer complexes.3--8 Indeed, this behavior has made possible the isolation of crystalline sodium (1) (a) Texas A & M University; (b) University of Tennessee. (2) For recent reviews on Meisenheimer complexes and their relevance in nucleophilic aromatic substitution, see (a) R. Foster and C. A. Fyfe, Rev. Pure Appl. Chem., 16, 61 (1966); (b) E. Buncel, A. R. Norris, and K . E. Russell, Quart. Rev., Chem. SOC.,22, 123 (1968); (c) P. Buck, Angew. Chem., Int. Ed. En&, 8, 120 (1969); (d) J. Miller, "Aromatic Nucleophilic Substitutions," Elsevier, Amaterdam, 1968; (e) M. R. Crampton, Aduan. Phys. O w . Chem., 7 , 211 (1969); (f) F. Pietra, Quart. Rev., Chem. SOC.,28, 604 (1969); (9) M. J. Strauss, Chem. Rev., TO, 667 (1970). (3) W. E. Byrne, E. J. Fendler, J. H. Fendler, and C. E. Griffin, J . 0 ~ 0 . Chem., 82, 2606 (1967). (4) E. J. Fendler, J. H. Fendler, W. E. Byrne, and C. E. Griffin, i b X , 8, 4141 (1968). (6) J. H. Fendler, E. J. Fendler, and C. E. Griffin, ibid., 84, 689 (1969). (6) E. J. Fendler, J. H. Fendler, C. E. Griffin, and J. W. Larsen, i b i d . , 86, 287 (1970). (7) G. 9. Gitis, A. I . Glaz. and A. Y. Kaminskii, J . Uen. Chem. USSR, 3229 (1963); 8. Nagakura, Tetrahedron, SuppZ., 19, No. 2, 361 (1963). (8) J. W. Larsen, K. Amin, and J. H . Fendler, J . Amer. Chem. Soc., 98, 2910 (1971). Determinations of heats of transfer of sodium methoxide, the Meisenheimer complex, sodium picrate, and 2,4,6-trinitroanisole from methanol to methanolic dimethyl sulfoxide solutions are reported.
and potassium cy~lohexadienylides.~-7We have demonstrated recently that the increase in the equilibrium constant for the formation of sodium 1,l-dimethoxy2,4-dicyano-6-nitrocyclohexadienylide(1) (eq 1) with increasing DMSO concentration in the DMSO-MeOH solvent system is due to an increase in the rate constant for complex formation (Icl) and a decrease in the rate constant for the decomposition of the complex (k2).6 These results have been rationalized using the differences in the hydrogen-bonding power of these solvents. Methoxide ions, being strong hydrogen bond acceptors, become considerably less solvated and, therefore, stronger nucleophiles in dipolar aprotic DMSO than in protic methano18i0 Since the 2,4,6-trinitroanisole is not effected strongly by this solvent change, kl increases with increasing DMSO concentration. The decrease in the rate constant for the decomposition of the complex (k2) with increasing DNSO concentration is probably caused by the greater solvation of the highly delocalized negative charge of the complex in (9) A. J . Parker, Quart. Reo., Chem. SOC.,16, 163 (1962); Aduan. Org. Chem., 5, l(1965); Aduan. Phys. Org. Chem., 5, 173 (1967); Chem. Rev., 69, l(l969).
